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A large study of mortality in Cushing’s syndrome calculated a threefold higher mortality rate for these patients, with cerebrovascular and atherosclerotic vascular diseases and infection accounting for 50% of deaths, researchers reported. “[We have seen] improvement in outcome since 2000, but mortality is still unacceptably high,” Padiporn Limumpornpetch, MD, an endocrinologist at Prince of Songkla University in Thailand and PhD student at the University of Leeds, U.K., told Healio during the ENDO annual meeting. “The mortality outcome has shown an unacceptable standardized mortality rate of 3:1, with poorer outcomes in patients with adrenal Cushing’s [and] active and larger tumors in Cushing’s disease.” Atherosclerotic vascular disease was the top cause of death in Cushing's disease, with infection coming in as the second-highest cause of death. Data were derived from Limumpornpetch P. OR04-4. Presented at: ENDO annual meeting; March 20-23, 2021 (virtual meeting). For a meta-analysis and meta-regression analysis of cause of death among patients with benign endogenous Cushing’s syndrome, Limumpornpetch and colleagues reviewed data published from 1952 to January 2021 from 92 study cohorts with 19,181 patients that reported mortality rates, including 66 studies that reported causes of death. The researchers calculated the standardized mortality rate (SMR) for Cushing’s syndrome at 3 (95% CI, 2.3-3.9). For patients with adrenal Cushing’s syndrome, SMR was 3.3 (95% CI, 0.5-6.6) — higher than for those with Cushing’s disease, with an SMR of 2.8 (95% CI, 2.1-3.7). Rates were similar by sex and by type of adrenal tumor. Deaths occurring within 30 days of surgery for Cushing’s syndrome fell to 3% after 2000 from 10% before that date (P < .005). During the entire study period, atherosclerotic vascular disease accounted for 27.4% of deaths in Cushing’s syndrome, and 12.7% were attributable to infection, 11.7% to cerebrovascular diseases, 10.6% to malignancy, 4.4% to thromboembolism, 2.9% to active disease, 3% to adrenal insufficiency and 2.2% to suicide. “We look forward to the day when our interdisciplinary approach to managing these challenging patients can deliver outcomes similar to the background population,” Limumpornpetch said. From https://www.healio.com/news/endocrinology/20210322/mortality-rate-in-cushings-syndrome-unacceptably-high
A retrospective cohort study was performed to compare mortality risk and causes of death in adrenal insufficiency with an individually-matched reference population. Researchers examined 6,821 patients with adrenal insufficiency (primary, 2052; secondary, 3948) and 6,7564 individually-matched controls (primary, 20366; secondary, 39134). It was shown that in adrenal insufficiency, mortality was elevated, particularly primary, even with individual matching, and was found early in the disease course. The data demonstrated that cardiovascular disease was the major cause but mortality from infection was also high. The adrenal crisis was a common contributor. The outcomes suggested that early education for prompt treatment of infections and avoidance of adrenal crisis hold the potential to decrease mortality. The Journal of Clinical Endocrinology & Metabolism, dgab096, https://doi.org/10.1210/clinem/dgab096 Abstract Context Mortality data in patients with adrenal insufficiency are inconsistent, possibly due to temporal and geographical differences between patients and their reference populations. Objective To compare mortality risk and causes of death in adrenal insufficiency with an individually-matched reference population. Design Retrospective cohort study. Setting UK general practitioner database (CPRD). Participants 6821 patients with adrenal insufficiency (primary, 2052; secondary, 3948) and 67564 individually-matched controls (primary, 20366; secondary, 39134). Main outcome measures All-cause and cause-specific mortality; hospital admission from adrenal crisis. Results With follow-up of 40799 and 406899 person-years for patients and controls respectively, the hazard ratio (HR; [95%CI]) for all-cause mortality was 1.68 [1.58 - 1.77]. HRs were greater in primary (1.83 [1.66 - 2.02]) than in secondary (1.52 [1.40 - 1.64]) disease; (HR; primary versus secondary disease, 1.16 [1.03 - 1.30]). The leading cause of death was cardiovascular disease (HR 1.54 [1.32-1.80]), along with malignant neoplasms and respiratory disease. Deaths from infection were also relatively high (HR 4.00 [2.15 - 7.46]). Adrenal crisis contributed to 10% of all deaths. In the first two years following diagnosis, the patients’ mortality rate and hospitalisation from adrenal crisis were higher than in later years. Conclusion Mortality was increased in adrenal insufficiency, especially primary, even with individual matching and was observed early in the disease course. Cardiovascular disease was the major cause but mortality from infection was also high. Adrenal crisis was a common contributor. Early education for prompt treatment of infections and avoidance of adrenal crisis hold potential to reduce mortality. PDF available at https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgab096/6141434?redirectedFrom=fulltext
Cushing’s disease patients in Sweden have a higher risk of death than the general Swedish population, particularly of cardiovascular complications, and that increased risk persists even in patients in remission, a large nationwide study shows. The study, “Overall and disease-specific mortality in patients with Cushing’s disease: a Swedish nationwide study,” was published in the Journal of Clinical Endocrinology and Metabolism. The outcomes of Cushing’s disease patients have improved with the introduction of several therapeutic approaches, such as minimally invasive surgery and cortisol-lowering therapies. However, mortality is still high, especially among those who do not achieve remission. While currently patients in remission are thought to have a better prognosis, it is still unclear whether these patients still have a higher mortality than the general population. Understanding whether these patients are more likely to die and what risk factors are associated with increased mortality is critical to reduce death rates among Cushing’s patients. A team of Swedish researchers thus performed a retrospective study that included patients diagnosed with Cushing’s disease who were part of the Swedish National Patient Registry between 1987 and 2013. A total of 502 patients with Cushing’s disease were included in the study, 419 of whom were confirmed to be in remission. Most patients (77%) were women; the mean age at diagnosis was 43 years, and the median follow-up time was 13 years. During the follow-up, 133 Cushing’s patients died, compared to 54 expected deaths in the general population — a mortality rate 2.5 times higher, researchers said. The most common causes of death among Cushing’s patients were cardiovascular diseases, particularly ischemic heart disease and cerebral infarctions. However, infectious and respiratory diseases (including pneumonia), as well as diseases of the digestive system, also contributed to the increased mortality among Cushing’s patients. Of those in remission, 21% died, compared to 55% among those not in remission. While these patients had a lower risk of death, their mortality rate was still 90% higher than that of the general population. For patients who did not achieve remission, the mortality rate was 6.9 times higher. The mortality associated with cardiovascular diseases was increased for both patients in remission and not in remission. Also, older age at the start of the study and time in remission were associated with mortality risk. “A more aggressive treatment of hypertension, dyslipidemia [abnormal amount of fat in the blood], and other cardiovascular risk factors might be warranted in patients with CS in remission,” researchers said. Of the 419 patients in remission, 315 had undergone pituitary surgery, 102 had had their adrenal glands removed, and 116 had received radiation therapy. Surgical removal of the adrenal glands and chronic glucocorticoid replacement therapy were associated with a worse prognosis. In fact, glucocorticoid replacement therapy more than twice increased the mortality risk. Growth hormone replacement was linked with better outcomes. In remission patients, a diagnosis of diabetes mellitus or high blood pressure had no impact on mortality risk. Overall, “this large nationwide study shows that patients with [Cushing’s disease] continue to have excess mortality even after remission,” researchers stated. The highest mortality rates, however, were seen in “patients with persistent disease, those who were treated with bilateral adrenalectomy and those who required glucocorticoid replacement.” “Further studies need to focus on identifying best approaches to obtaining remission, active surveillance, adequate hormone replacement and long-term management of cardiovascular and mental health in these patients,” the study concluded. From https://cushingsdiseasenews.com/2019/02/28/even-in-remission-cushings-patients-have-excess-mortality-swedish-study-says/